Peripheral arterial disease currently afflicts approximately eight million Americans (Statistical Fact Sheet, 2004, http://www.americanheart.org/presenter.jhtml?identifier=2021), a number expected to rapidly increase as the population ages and becomes more susceptible to cardiovascular disease. Currently, more than 450,000 coronary artery bypass graft procedures are performed each year (Mitchell S L, and Niklason L E, 2003, Cardiovasc Pathol 12(2):59-64). The ‘gold standard’ of care in these cases is autologous grafting, where a suitable vein or artery from another site of the body (typically a lower limb or the internal mammary artery) is removed and used to bypass the diseased vein or artery. However, in cases where the patient has a particularly complex arterial disease, has previously failed endovascular procedures, or does not have suitable vessels to harvest, synthetic or tissue-engineered vessels can provide an alternative (Baguneid M S, et al., 2006, Br J Surg. 93(3):282-290).
Clinically, two of the more successful synthetic vascular graft materials are expanded polytetrafluoroethylene (ePTFE, Teflon®) and polyethylene terephthalate (PET, Dacron®) (Kannan R Y, et al., 2005, Biomaterials 26(14):1857-1875). When modified with an anticoagulant such as heparin, or seeded with endothelial cells to generate a tissue-engineered vessel, these synthetic graft materials approach the ‘gold standard’ of 75% for 5-year patency of autologous vein grafts in human trials (Baguneid M S, et al., 2006, Br J Surg. 93(3):282-290; Meinhart J G, et al., 2001, Ann Thorac Surg. 71(5 Suppl):S327-331; Lambert A W, et al., 1999, Cardiovasc Surg. 7(5):491-494). These results, however, were only achieved for relatively larger diameter grafts (6 to 7 mm inner diameter, ID). When synthetic materials such as unmodified PTFE are used as a microvascular graft for vessels less than 1 mm in diameter, the patency rate drops below this ‘gold standard’(Harris J R and Seikaly H, 2002, J Otolaryngol 31(2):89-92). In fact, while heparin-bonded ePTFE macrovascular grafts are commercially available in Europe and have recently been approved by the U.S. Food & Drug Administration (FDA clears GORE PROPATEN vascular graft, 2006 [cited Feb. 19, 2007], http://www.goremedical.com/press/news/propaten-uslaunch2006), no microvascular graft (natural, synthetic, or tissue-engineered) has been fully accepted into routine clinical practice, leaving significant room for improvement in the field (Bosiers M, et al., 2006, J Vasc Surg. 43(2):313-318; discussion 318-319; Heyligers J M, et al., 2006, J Vasc Surg. 43(3):587-591).
Silk coated substrates and the use of silk coatings for the delivery of drugs or other bioactive agents is described in WO 2007/016524.